Preliminary observations have indicated an unusually high incidence of inherited deficiency of two complement components, C6 and C2, in patients with membranoproliferative glomerulonephritis (MPGN). Heterozygous deficiency of C2 occured in 7-12 percent and homozygous and heterozygous deficiency of C6 was present in 15 to 20 percent of patients with Type I MPGN. The incidence of these deficiencies in patients with other forms of glomerulonephritis, both acute and chronic, and in the general population will be determined. This aspect of the study suggests a multifactorial genetic origin of MPGN and is reminiscent of the observation that heterozygous deficiency of C2 occurs with significantly greater frequency in patients with lupus than in the general population. Another facet of the study will be pursuit of the chance observation of a pedigree in which there is dual heterozygous deficiency of the C3b inactivator (C3bINA) and C6 in a father and two of six children; the mother and the remaining children have normal levels. An effort will be made to gain further evidence for a linkage relationship between these two proteins. In this study, attempts will be made to detect inherited electrophoretic variants of C3bINA as well as of other proteins controlling the C3b feedback, beta 1H the C4 binding protein, to gain evidence for or against linkage between these loci and that for C6. These studies will be largely performed on five families we have encountered with C6d. Finally, the nature of an inherited defect, characterized by half-normal levels of C3 and factor B, thought to be due to a defect in C3b feedback control, present in five members of three generations of a family, will be investigated. Two of the five family members have chronic glomerulonephritis and three of them have had recurrent infections in childhood. Evidence for abnormalities in the function of the C3b feedback control proteins as well as in the component proteins, C3 and factor B, will be sought.